1. the molecular basis of T3 dependent gene activation as studied utilizing nuclear extracts prepared from Spodoptera frugiperda cells infected with recombinant baculovirus overexpressing rat thyroid hormone receptor (rTRalpha) and H2RIIBP. We showed that rTRalpha homodimerizes in solution, binds the hormone and both liganded and unliganded receptor homodimer interacts with an 18 bp region of the promoter of the malic enzyme gene (ME-TRE) as a homodimer. Furthermore the receptor formed heterodimers with either in solution or on the TRE, H-2RIIBP a non-hormone binding member of the steroid hormone receptor superfamily, when present in nuclear extract prepared from Sf9 cells infected with a recombinant baculovirus overexpressing H-2RIIBP. Heterodimerization occurred at a higher rate than did homodimerization of either rTRalpha or H-2RIIBP. Heterodimerization was an important component of rTRalpha binding to TH and the ME-TRE since both were increased several fold when rTRalpha was allowed to heterodimerize with H-2RIIBP. Quantitative analysis of TH binding not only demonstrated the ability of the heterodimer to bind TH but also revealed that the heterodimer bound the same amount of TH as the homodimer did, suggesting a stoichiometry of 1 ligand per dimeric species. Interestingly, a heterodimer of rTRalpha and a rat liver nuclear protein was incapable of binding TH. Finally, the functional data demonstrated that cotransfection of plasmids expressing H-2RIIBP and rTRalpha increased the TH inducibility of ME-TRE over that observed with the rTRalpha alone. These results imply that thyroid hormone inducibility depends on the nature of rTRalpha dimeric species which in turn affects interaction with TREs. 2. We analyzed and determined sequences in the thyroid hormone receptor gene which are required for the promoter activity of this gene.